Hydrogen-bonding patterns in 3-alkyl-3-hydroxyindolin-2-ones

Abstract

The molecules of racemic 3-benzoylmethyl-3-hydroxyindolin-2-one, C(16)H(13)NO(3), (I), are linked by a combination of N-H...O and O-H...O hydrogen bonds into a chain of centrosymmetric edge-fused R(2)(2)(10) and R(4)(4)(12) rings. Five monosubstituted analogues of (I), namely racemic 3-hydroxy-3-[(4-methylbenzoyl)methyl]indolin-2-one, C(17)H(15)NO(3), (II), racemic 3-[(4-fluorobenzoyl)methyl]-3-hydroxyindolin-2-one, C(16)H(12)FNO(3), (III), racemic 3-[(4-chlorobenzoyl)methyl]-3-hydroxyindolin-2-one, C(16)H(12)ClNO(3), (IV), racemic 3-[(4-bromobenzoyl)methyl]-3-hydroxyindolin-2-one, C(16)H(12)BrNO(3), (V), and racemic 3-hydroxy-3-[(4-nitrobenzoyl)methyl]indolin-2-one, C(16)H(12)N(2)O(5), (VI), are isomorphous in space group P-1. In each of compounds (II)-(VI), a combination of N-H...O and O-H...O hydrogen bonds generates a chain of centrosymmetric edge-fused R(2)(2)(8) and R(2)(2)(10) rings, and these chains are linked into sheets by an aromatic pi-pi stacking interaction. No two of the structures of (II)-(VI) exhibit the same combination of weak hydrogen bonds of C-H...O and C-H...pi(arene) types. The molecules of racemic 3-hydroxy-3-(2-thienylcarbonylmethyl)indolin-2-one, C(14)H(11)NO(3)S, (VII), form hydrogen-bonded chains very similar to those in (II)-(VI), but here the sheet formation depends upon a weak pi-pi stacking interaction between thienyl rings. Comparisons are drawn between the crystal structures of compounds (I)-(VII) and those of some recently reported analogues having no aromatic group in the side chain.

Autoxidation/Aldol Tandem Reaction of 2‐Oxindoles with Ketones: A Green Approach for the Synthesis of 3‐Hydroxy‐2‐Oxindoles

“…2-Oxindoles are not only one of the promising drug candidates buta lso useful starting materials for the synthesis of natural products. [5] The direct transformation of 2-oxindoles has been widely used in organic synthesis, in which various kinds of chemical bonds could be constructed by the oxidation, halogenation and addition process through CÀHb ond cleavage. [6] For instance, 3-hydroxy-2-oxindoles, which are frequently observedi nb ioactive natural products,c an be produced directly from the corresponding 3-subsituted 2-oxindoles by hydroxylation or amino-oxygenation reactions (Scheme 1).…”

Synthesis of Novel Pyrimido[4,5-b]quinolin-4-ones with Potential Antitumor Activity

“…The 9 E ‐configuration was determined on the basis of the NOESY experiment, which showed the correlation between the ═CH and NH amine protons and confirmed by X‐ray diffraction analysis (Fig. ) .…”

Synthesis of N-substituted 3-(2-aryl-2-oxoethyl)-3-hydroxyindolin-2-ones and their conversion to N-substituted (E)-3-(2-aryl-2-oxoethylidene)indolin-2-ones: synthetic sequence, spectroscopic characterization and structures of four 3-hydroxy compounds and five oxoethylidene products

“…By contrast, the structure of pyridyl derivative (Ie) contains no O-HÁ Á ÁO hydrogen bonds (Table 2). It is interesting in this context to note that in a series of seven 3-alkyl-3-hydroxyindolin-2-ones, having no substituent on the N atom of the indoline ring, every structure contains a centrosymmetric R 2 2 (10) ring embedded within a more complex supramolecular assembly involving N-HÁ Á ÁO hydrogen bonds and, in some cases, C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds also (Becerra et al, 2010). Rings of the R 2 2 (10) type also occur in a number of related examples in the Cambridge Structural Database (CSD; Groom et al, 2016), including examples having CSD refcodes MUMMAY (Chen et al, 2009), TAWFAZ (Luppi et al, 2005), TEQVUH (Luppi et al, 2006) and YIFZIX (Xing et al, 2007).…”

“…Several years ago, we reported the synthesis and structures of a range of 3-alkyl-3-hydroxyindolin-2-ones by reaction of isatin itself with a variety of methyl ketones in the presence of piperidine. Although the procedures were straightforward, the yields were consistently rather disappointing, in the range 40-60% (Becerra et al, 2010). Within the isatin molecule, both simple amide and vinylogous amide fragments can be identified, so that in the conjugate base of isatin the negative charge can be delocalized into both carbonyl groups.…”